Document Detail


Mutational analyses of multiple oncogenic pathways in intraductal papillary mucinous neoplasms of the pancreas.
MedLine Citation:
PMID:  18376308     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: There is much accumulated evidence that EGFR, HER2, and their downstream signaling pathway members such as KRAS, BRAF, and PIK3CA are strongly implicated in cancer development and progression. Recently, mutations in the kinase domains of EGFR and HER2, associated with increased sensitivity to tyrosine kinase inhibitors, have been described.
METHODS: To evaluate the mutational status of these genes in intraductal papillary mucinous neoplasm (IPMN)/intraductal papillary mucinous carcinoma (IPMC), EGFR and HER2 were analyzed in 36 IPMN/IPMC, and the results were correlated to the mutational status of the KRAS, BRAF, and PIK3CA genes in the samples.
RESULTS: Together, we identified 1 silent mutation of HER2, 17 (43%) KRAS mutations, 1 (2.7%) BRAF mutation, and 4 (11%) mutations of PIK3CA in the IPMN/IPMC samples.
CONCLUSIONS: The EGFR and ERBB2 (HER2) mutations are very infrequent in IPMN/IPMC, suggesting the limited possibility of targeting mutated ERBB2 and EGFR for therapy for these lesions. The KRAS, BRAF, and PIK3CA, however, could represent interesting targets for future therapies in these lesions.
Authors:
Frank Schönleben; John D Allendorf; Wanglong Qiu; Xiaojun Li; Daniel J Ho; Nancy T Ciau; Robert L Fine; John A Chabot; Helen E Remotti; Gloria H Su
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Pancreas     Volume:  36     ISSN:  1536-4828     ISO Abbreviation:  Pancreas     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-03-31     Completed Date:  2008-06-19     Revised Date:  2012-06-21    
Medline Journal Info:
Nlm Unique ID:  8608542     Medline TA:  Pancreas     Country:  United States    
Other Details:
Languages:  eng     Pagination:  168-72     Citation Subset:  IM    
Affiliation:
Department of Otolaryngology/Head and Neck Surgery, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma, Mucinous / enzymology,  genetics*,  mortality,  pathology
Aged
Aged, 80 and over
Carcinoma, Intraductal, Noninfiltrating / enzymology,  genetics*,  mortality,  pathology
Cohort Studies
Female
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic*
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Mutation*
Neoplasm Staging
Oncogenes*
Pancreatic Neoplasms / enzymology,  genetics*,  mortality,  pathology
Phosphatidylinositol 3-Kinases / genetics
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins B-raf / genetics
Receptor, Epidermal Growth Factor / genetics
Receptor, erbB-2 / genetics
ras Proteins / genetics
Grant Support
ID/Acronym/Agency:
CA95434/CA/NCI NIH HHS; K01 CA095434-05/CA/NCI NIH HHS; R01 CA109525/CA/NCI NIH HHS; R01 CA109525-03/CA/NCI NIH HHS; R01 CA109525-04/CA/NCI NIH HHS; R01 CA109525-05/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/KRAS protein, human; 0/Proto-Oncogene Proteins; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.1.137/PIK3CA protein, human; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/ERBB2 protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.10.1/Receptor, erbB-2; EC 2.7.11.1/BRAF protein, human; EC 2.7.11.1/Proto-Oncogene Proteins B-raf; EC 3.6.5.2/ras Proteins

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